The effect of 2-mercapto-5-methyl-1,3,4-thiadiazole on enzymatic synthesis of cefazolin.
The effect of unreacted residual 2-mercapto-5-methyl-1,3,4-thiadiazole (MMTD), the reagent for 3-[5-methyl-1,3,4-thiadiazole-2-yl]-7-aminocephalosporanic acid (M-7-ACA) synthesis, on the enzymatic acylation of M-7-ACA by the methyl ester of 1,2,3,4-tetrazol-1-acetic acid (MeTzAA) to produce cefazolin (CEZ) was studied. In the two-step process of synthesizing CEZ from 7-aminocephalosporanic acid (7-ACA), one of the key parameters controlling the overall CEZ yield was the ratio of MMTD to 7-ACA in M-7-ACA synthesis. The increase of the ratio showed opposing effects by increasing the M-7-ACA yield in the first step, while decreasing CEZ yield in the subsequent enzymatic reaction by the inhibitory effect of the increased content of MMTD as an impurity in the M-7-ACA preparation. It was revealed that the decrease of CEZ yield in the enzymatic reaction was caused by the selective retardation of the rate of CEZ synthesis reaction by a typical competitive inhibition, while not affecting the rate of MeTzAA hydrolysis reaction. The optimum MMTD-to-7-ACA ratio rendering the highest overall CEZ yield over 7-ACA was 1.2:1.
Won
J I
JI
Cheil Jedang Corp., R & D Center, Kyonggi-do, Korea.
Kim
C G
CG
Kim
J H
JH
Lee
J H
JH
Jeon
Y J
YJ
D002384:Catalysis; D002437:Cefazolin / Q000138:chemical synthesis*; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000737:chemistry*; D004800:Enzymes, Immobilized / Q000737:chemistry*; D006868:Hydrolysis; D010399:Penicillin Amidase / Q000737:chemistry; D013830:Thiadiazoles / Q000737:chemistry*
D002511:Cephalosporins; D004800:Enzymes, Immobilized; D013830:Thiadiazoles; C049131:2-methyl-1,3,4-thiadiazole-5-thiol; C030735:7-aminocephalosporanic acid; D010399:Penicillin Amidase; D002437:Cefazolin